The objectives of this project are to: 1) identify the sequences in the viral genome that convey oncogenecity to the recombinant murine leukemia viruses produced by inbred strains of mice; 2) determine the origins of such sequences; and 3) define the biologic role of these sequences in mediating oncogenesis. We will follow the pattern of expression of leukemogenic virus-related sequences in viruses derived from preleukemic mice by T1-oligonucleotide fingerprinting of the viral RNA. We will also molecularly clone the DNA of viruses produced by preleukemic AKR/J mice. The cloned viruses can then be sequenced and the regions of the genome important for leukemogenecity can be determined. To find the source of these sequences we will survey the genomic structure of viruses produced by defined endogenous proviral loci that are present in the DNA of mice. We will attempt to detect defective RNA products that contain leukemogenic virus-related sequences by exploiting northern blotting, hybridization selection, and RNA fingerprinting techniques. Finally, we will conduct biologic testing of selected viruses and genetically engineered recombinants. These experiments will help determine the biologic role of the leukemogenic virus-related sequence in these viruses, such as regulating target organ specificity, rapid replication in vivo, and/or the oncogenic transformation event itself.